Epidemiological studies of colon cancer have called attention to diet and the intestinal flora as major etiologic factors in this disease. In this study an effort will be made to elucidate the mechanisms by which diet influences the incidence of colon cancer with particular reference to metabolic activities of the intestinal microflora. Rats will be placed on 1) a cereal diet, 2) a high animal protein diet, 3) a high animal protein and fat diet. Animals will be sacrificed at various intervals and measurements will be made of enzyme levels in the intestinal mucosa and the microflora. The enzymes selected for analysis have been shown to be involved in the activation of procarcinogens to carcinogens. These include beta-glucuronidase, beta-glucosidase, N-aryl hydroxylase, phosphosulfotransferase and nitro- reductase. In addition, the levels of aryl sulfatase and N-aryl dehydroxylase will be measured; these enzymes are believed to detoxify carcinogens. The proposed study consists of two parts. The first part will investigate the effects of diet on specific bacterial and mucosal enzymes involved in activation or detoxification of chemical carcinogens. The second part will extend these studies by administering chemical carcinogens, azoxymethane and 3,2' dimethyl-4-aminobiphenyl (DMAB), to animals receiving these diets and subsequently monitoring tumor induction and enzyme activity. These carcinogens are known to require specific enzymes for activation or retoxification. The data will be analyzed with regard to the influence of diet in regulating bacterial or mucosal enzymes involved in chemical carcinogenesis. In addition, the relation between dietary-induced enzyme changes and the incidence of colon cancer in rats exposed to specific procarcinogens will be determined. Finally, we will observe whether the administration of procarcinogens can cause metabolic adaptation of the specific mucosal and bacterial enzymes involved in their activation or detoxification.